Forkhead box A1 transcriptional pathway in KRT7-expressing esophageal squamous cell carcinomas with extensive lymph node metastasis

  • Authors:
    • Masayuki Sano
    • Kazuhiko Aoyagi
    • Hiro Takahashi
    • Takeshi Kawamura
    • Tomoko Mabuchi
    • Hiroyasu Igaki
    • Yuji Tachimori
    • Hoichi Kato
    • Atsushi Ochiai
    • Hiroyuki Honda
    • Yuji Nimura
    • Masato Nagino
    • Teruhiko Yoshida
    • Hiroki Sasaki
  • View Affiliations

  • Published online on: February 1, 2010     https://doi.org/10.3892/ijo_00000503
  • Pages: 321-330
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )


Abstract

Prognosis of cancers with lymph node metastasis is known to be very poor; however, it is still controversial whether metastatic potential can be evaluated by expression profiles of primary tumors. Therefore, to address this issue, we compared gene expression profiles of 24 esophageal squamous cell carcinomas (ESCCs) with extensive lymph node metastasis and 11 ESCCs with no metastatic lymph node. However, there was no gene cluster distinguishing these two groups, suggesting that lymph node metastasis-associated genes are varied depending on cases or subgroups. Therefore, we applied a recently developed filtering method (S2N') to identify such genes, and successfully extracted 209 genes associated with node status. Among them, over-expression of CALB1, KRT7/CK7, MUC1 and CEA/CEACAM5 in poor prognostic cases with metastatic lymph nodes was confirmed in two sets of ESCCs by RT-PCR. Each often seemed to have glandular cell type-characteristics in both the gene expression and morphology. It was also revealed that FOXA1 siRNA treatment of esophageal cancer cells reduced the mRNA level of both KRT7 and a stabilizer of epithelial-mesenchymal transition (EMT) regulator LOXL2, and that both FOXA1 and LOXL2 siRNAs reduced invasion and migration of ESCC cells. In 15 KRT7-expressing ESCCs with metastatic lymph nodes, 60% expressed FOXA1 and 33% expressed both FOXA1 and LOXL2. These results suggest that FOXA1 induces not only KRT7 but also LOXL2 in a subset of poor prognostic ESCCs with metastatic lymph nodes, and it is also plausible, that other FOXA1 downstream genes could be therapeutic targets of poor prognostic ESCCs.

Related Articles

Journal Cover

February 2010
Volume 36 Issue 2

Print ISSN: 1019-6439
Online ISSN:1791-2423

Sign up for eToc alerts

Recommend to Library

Copy and paste a formatted citation
x
Spandidos Publications style
Sano M, Aoyagi K, Takahashi H, Kawamura T, Mabuchi T, Igaki H, Tachimori Y, Kato H, Ochiai A, Honda H, Honda H, et al: Forkhead box A1 transcriptional pathway in KRT7-expressing esophageal squamous cell carcinomas with extensive lymph node metastasis. Int J Oncol 36: 321-330, 2010
APA
Sano, M., Aoyagi, K., Takahashi, H., Kawamura, T., Mabuchi, T., Igaki, H. ... Sasaki, H. (2010). Forkhead box A1 transcriptional pathway in KRT7-expressing esophageal squamous cell carcinomas with extensive lymph node metastasis. International Journal of Oncology, 36, 321-330. https://doi.org/10.3892/ijo_00000503
MLA
Sano, M., Aoyagi, K., Takahashi, H., Kawamura, T., Mabuchi, T., Igaki, H., Tachimori, Y., Kato, H., Ochiai, A., Honda, H., Nimura, Y., Nagino, M., Yoshida, T., Sasaki, H."Forkhead box A1 transcriptional pathway in KRT7-expressing esophageal squamous cell carcinomas with extensive lymph node metastasis". International Journal of Oncology 36.2 (2010): 321-330.
Chicago
Sano, M., Aoyagi, K., Takahashi, H., Kawamura, T., Mabuchi, T., Igaki, H., Tachimori, Y., Kato, H., Ochiai, A., Honda, H., Nimura, Y., Nagino, M., Yoshida, T., Sasaki, H."Forkhead box A1 transcriptional pathway in KRT7-expressing esophageal squamous cell carcinomas with extensive lymph node metastasis". International Journal of Oncology 36, no. 2 (2010): 321-330. https://doi.org/10.3892/ijo_00000503